These studies are designed to determine whether hydroxyurea, a cytotoxic agent, will cause significant production of HbF in patients with sickle cell anemia. Studies in experimental animals have shown modest but significant increases in HbF synthesis after drug treatment. We have administered the drug in varying doses and at different intervals to ten patients with sickle cell anemia. High doses employed initially (50mg/kg) caused significant hematopoietic toxicity in some patients. Analysis of peak drug levels and the rate of clearance following a single oral dose uncovered significant heterogenity among patients; marrow depression occurred in patients with the highest levels and the slowest rate of clearance. Subsequent readjustment of the dose based on pharmacokinetic measurements allowed us to avoid toxicity. The most effective regimen employed to date is the administration of 40-50mg/kg once per week. On this schedule, several patients have exhibited a progressive increase in HbF synthesis to 6-12%. Two additional patients with severe beta thalassemia have been treated. Once exhibited a modest response with a reticulocytosis and stabilization of the Hb concentration.